Requirement of the JNK-associated Bcl-2 pathway for human lactoferrin-induced apoptosis in the Jurkat leukemia T cell line

Lee, Shin Hee; Park, Sang Won; Pyo, Chul Woong; Yoo, Na Kyung; Kim, Jiyoung; Choi, Seo‐Hyun

doi:10.1016/j.biochi.2008.05.004

Cited by 48 publications

(53 citation statements)

References 21 publications

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“…Recent studies suggest that JNK may induce apoptosis via modulating the proapoptotic Bcl-2 protein BIM (41). Bcl-2 itself, an inhibitor of apoptosis, is phosphorylated by the ASK-1/JNK pathway to its inactive form, resulting in increased susceptibility to apoptosis in Jurkat cells (38,40). We observed significant caspase cleavage ( Figures 4A and 4B), PARP-1 cleavage ( Figures 4A and 4C), and TUNEL-positive cells ( Figures 5A and 5B) in the LIC-WT condition that were prevented in LIC-ko mice.…”

Section: Ask-1 and Apoptosismentioning

confidence: 75%

“…JNK phosphorylates not only c-Jun (32) but also other transcription (33)(34)(35)(36) and nontranscription factors, such as the B cell lymphoma-2 (Bcl-2) family (37)(38)(39). Through its actions on Bcl-2 proteins, JNK can either inhibit (39) or promote (38,40) apoptosis. Recent studies suggest that JNK may induce apoptosis via modulating the proapoptotic Bcl-2 protein BIM (41).…”

Section: Ask-1 and Apoptosismentioning

confidence: 99%

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Deletion of Apoptosis Signal–Regulating Kinase–1 Prevents Ventilator-Induced Lung Injury in Mice

Makena¹,

Gorantla²,

Ghosh³

et al. 2012

Am J Respir Cell Mol Biol

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Both hyperoxia and mechanical ventilation can independently cause lung injury. In combination, these insults produce accelerated and severe lung injury. We recently reported that pre-exposure to hyperoxia for 12 hours, followed by ventilation with large tidal volumes, induced significant lung injury and epithelial cell apoptosis compared with either stimulus alone. We also reported that such injury and apoptosis are inhibited by antioxidant treatment. In this study, we hypothesized that apoptosis signal-regulating kinase-1 (ASK-1), a redox-sensitive, mitogen-activated protein kinase kinase kinase, plays a role in lung injury and apoptosis in this model. To determine the role of ASK-1 in lung injury, the release of inflammatory mediators and apoptosis, attributable to 12 hours of hyperoxia, were followed by large tidal volume mechanical ventilation with hyperoxia. Wild-type and ASK-1 knockout mice were subjected to hyperoxia (FI O 2 ¼ 0.9) for 12 hours before 4 hours of large tidal mechanical ventilation (tidal volume ¼ 25 ml/g) with hyperoxia, and were compared with nonventilated control mice. Lung injury, apoptosis, and cytokine release were measured. The deletion of ASK-1 significantly inhibited lung injury and apoptosis, but did not affect the release of inflammatory mediators, compared with the wild-type mice. ASK-1 is an important regulator of lung injury and apoptosis in this model. Further study is needed to determine the mechanism of lung injury and apoptosis by ASK-1 and its downstream mediators in the lung.Keywords: ventilator-induced lung injury; acute lung injury; hyperoxia; apoptosis; apoptosis signal-regulating kinase-1 Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are destructive disorders that affect approximately 200,000 patients per year in the United States alone, with mortality as high as 60%. The resulting hypoxemic respiratory failure mandates the use of mechanical ventilation, putting patients at risk for ventilator-induced lung injury (VILI). At least 9% excess mortality has been attributed to VILI in these patients (1). Most patients with ARDS are mechanically ventilated using high concentrations of oxygen (mean FI O 2 on Day 1 ¼ 70%) (2). The most severely ill patients require a much higher FI O 2 (100%) for prolonged periods or for frequent intervals (3). Although both mechanical ventilation and hyperoxia (HO) have been extensively studied, surprisingly little attention has been paid to their potential interaction, despite their near ubiquitous concomitant use. Although high concentrations of oxygen combined with mechanical ventilation are often life-saving, hyperoxia in conjunction with mechanical ventilation can augment lung injury (4-9). We reported that pre-exposure to HO (FI O 2 ¼ 0.9 for 12 hours), followed by large tidal volume mechanical ventilation (HV ¼ 25 ml/g for 4 hours) with HO, caused significant lung injury compared with either stimulus alone or combined HV and HO not preceded by exposure ti HO (7). This severe lung injury was associated with ca...

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Section: Ask-1 and Apoptosismentioning

confidence: 75%

Section: Ask-1 and Apoptosismentioning

confidence: 99%

Deletion of Apoptosis Signal–Regulating Kinase–1 Prevents Ventilator-Induced Lung Injury in Mice

Makena¹,

Gorantla²,

Ghosh³

et al. 2012

Am J Respir Cell Mol Biol

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“…Other studies, for example, Lee et al (2009) and Ogino et al (2009), have demonstrated activation of the JNK pathway in Jurkat cells resulting in apoptosis using monochloramine, a neutrophil-derived oxidant, and lactoferrin, a iron-binding glycoprotein. In our study, ERK protein, which is associated with cell proliferation and survival, was activated with PA treatment (Yoon and Seger, 2006).…”

Section: Journal Of Cellular Physiologymentioning

confidence: 97%

Activation of survival and apoptotic signaling pathways in lymphocytes exposed to palmitic acid

Takahashi

Cambiaghi

Luchessi

et al. 2011

Journal Cellular Physiology

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The toxicity of palmitic acid (PA) towards a human T-lymphocyte cell line (Jurkat) has been previously investigated but the mechanism(s) of PA action were unknown. In the current study, Jurkat cells were treated with sub-lethal concentrations of PA (50-150µM) and the activity of various signaling proteins was investigated. PA-induced apoptosis and mitochondrial dysfunction in a dose-dependent manner as evaluated by DNA fragmentation assay and depolarization of the mitochondrial membrane, respectively. PA treatment provoked release of cytochrome c from the inner mitochondrial membrane to the cytosol, activated members of the MAPK protein family JNK, p38, ERK, activated caspases 3/9, and increased oxidative/nitrosative stress. Exposure of cells to PA for 12 h increased insulin receptor (IR) and GLUT-4 levels in the plasma membrane. Insulin treatment (10 mU/ml/30 min) increased the phosphorylation of the IR β-subunit and Akt. A correlation was found between DNA fragmentation and expression levels of both IR and GLUT-4. Similar results were obtained for PA-treated lymphocytes from healthy human donors and from mesenteric lymph nodes of 48-h starved rats. PA stimulated glucose uptake by Jurkat cells (in the absence of insulin), stimulated accumulation of neutral lipids (triglyceride), and other lipid classes (phospholipids and cholesterol ester) but reduced glucose oxidation. Our results suggest that parameters of insulin signaling and non-oxidative glucose metabolism are stimulated as part of a coordinated response to prompt survival in lymphocytes exposed to PA but at higher concentrations, apoptosis prevails. These findings may explain aspects of lymphocyte dysfunction associated with diabetes.

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“…Considering this, apoptosis clearly performs some crucial functions in the regulation of tumor progression. Previous studies have shown that Lf inhibits cell proliferation via cell cycle arrest or apoptosis (Lee et al 2009a;Son et al 2006). Lf concentration has also been implicated as crucial to the control of both cell survival and cell death.…”

Section: Introductionmentioning

confidence: 98%

E2F1-directed activation of Bcl-2 is correlated with lactoferrin-induced apoptosis in Jurkat leukemia T lymphocytes

et al. 2010

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Lactoferrin (Lf) has been shown to control the proliferation of a variety of mammalian cells. Recently, we reported that human Lf induces apoptosis via a c-Jun N-terminal kinases (JNK)-associated Bcl-2 pathway that stimulates programmed cell death. In order to gain insight into the mechanism underlying Lf-triggered apoptotic features, we attempted to determine the mechanisms whereby the Lf-induced Bcl-2 family proteins exert their pro- or anti-apoptotic effects in Jurkat leukemia T lymphocytes. Treatment of the cells with high concentrations of Lf resulted in a significant reduction in in vitro growth and cell viability. As the levels of Lf increased, greater quantities of CDK6 and hyper-phosphorylated retinoblastoma protein were produced, resulting in the induction of E2F1-dependent apoptosis. Simultaneously, PARP and caspases were efficiently cleaved during Lf-induced apoptosis. The E2F1-induced apoptotic process occurred preferentially in p53-deficient Jurkat leukemia cells. Therefore, we attempted to determine whether E2F1-regulated Bcl-2 family proteins involved in the apoptotic process were relevant to Lf-induced apoptosis. We found that Lf increased the interaction of Bcl-2 with the pro-apoptotic protein Bad, whereas the total protein levels did not change significantly. Our results, collectively, suggest that Lf exploits the control mechanism of E2F1-regulated target genes or Bcl-2 family gene networks involved in the apoptotic process in Jurkat human leukemia T lymphocytes.

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Requirement of the JNK-associated Bcl-2 pathway for human lactoferrin-induced apoptosis in the Jurkat leukemia T cell line

Cited by 48 publications

References 21 publications

Deletion of Apoptosis Signal–Regulating Kinase–1 Prevents Ventilator-Induced Lung Injury in Mice

Deletion of Apoptosis Signal–Regulating Kinase–1 Prevents Ventilator-Induced Lung Injury in Mice

Activation of survival and apoptotic signaling pathways in lymphocytes exposed to palmitic acid

E2F1-directed activation of Bcl-2 is correlated with lactoferrin-induced apoptosis in Jurkat leukemia T lymphocytes

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